Menopause, a natural phenomenon that occurs with aging in all women, is a significant health-relevant issue because the syndrome is accompanied by disrupted sleep patterns, inappropriate flushes and sweating, osteoporosis and enhanced cardiovascular malfunctions. Lowered estrogen secretion exacerbates these symptoms and thus estrogen therapy is a frequent prescribed treatment, although the sequence, cause and relevance of various symptoms to the overall syndrome is poorly understood. In large measure this is because suitable models to study this syndrome in women have not been identified. The goals of this project are to characterize endocrine and neural changes as they develop in perimenopausal rhesus macaque females and to demonstrate creative approaches to selective isolation of ovarian and hypothalamic components that contribute to "the menopausal syndrome" so the importance of each, first singularly and second collectively, can be studied. Procedures have been perfected to monitor changes in endogenous neurochemical secretions, neuropeptides and catecholamines from intact localized brain cells and, simultaneously to compare these profiles with a variety of peripheral plasma hormone patterns (gonadotropins, prolactin, growth hormone, thyroxine, cortisol, estradiol and progesterone) in rhesus macaques. To date, the research has focused on the nature of the hypothalamic signals that drive gonadotropin secretion during the primate menstrual cycle and in ovariectomized (OVX) females without and with pulsatile circulating steroids that simulate those in ovarian intact (INT) macaques. We now propose studies that will extend these findings to premenopausal individuals with ovarian (absence of secondary and tertiary follicles) and hypothalamic (block of NE neurons) deficits so that endocrine and neurosignalling mechanisms are better understood as indices of postmenopausal brain changes and psychological well-being.